Symbiotic Antidiabetic Effect of Lactobacillus casei and the Bioactive Extract of Cleome droserifolia (Forssk.) Del. on Mice with Type 2 Diabetes Induced by Alloxan.

The consumption of probiotics protects pancreatic ß-cells from oxidative damage, delaying the onset of type 2 diabetes mellitus (T2DM) and preventing microvascular and macrovascular complications. This study aimed to evaluate the antidiabetic activity of CDE fermented by Lactobacillus casei (ATCC 39539) (LC) in alloxan-induced diabetic rats. The oxidative stress identified by catalase (CAT), serum AST, ALT, ALP, creatinine, urea, and uric acid were measured. The chemical profiles of the plant extract and the fermented extract were studied using HPLC/MS. The potential of the compounds towards the binding pockets of aldose reductase and PPAR was discovered by molecular docking. A significant reduction in fasting blood glucose in alloxan-treated rats. The CAT showed a significant decrease in diabetic rats. Also, serum AST, ALT, ALP, creatinine, urea, and uric acid were significantly decreased in the mixture group. Mild histological changes of pancreatic and kidney tissues suggested that the mixture of probiotics and cleome possesses a marked anti-diabetic effect. Overall, the study suggests that the combination of Cleome droserifolia fermented by Lactobacillus casei exhibits significant antidiabetic activity (p-value=0.05), reduces oxidative stress, improves lipid profiles, and shows potential for the treatment of diabetes.

Metabolites Profiling and Bioassays Reveal Bassia indica Ethanol Extract Protective Effect against Stomach Ulcers Development via HMGB1/TLR-4/NF-κB Pathway.

Clinical manifestation of gastric ulcers is frequent, in addition to their costly drug regimens, warranting the development of novel drugs at lower costs. Although Bassia indica is well characterized for its anti-inflammatory and antioxidant potential, capacity of its ethanol extract (BIEE) to prevent stomach ulcers' progression has not been reported. A nuclear protein termed high-mobility group box 1 (HMGB1) plays a key role in the formation of stomach ulcers by triggering a number of inflammatory responses. The main purpose of the current investigation was to evaluate the in vivo anti-inflammatory and anti-ulcerogenic capabilities of BIEE against ethanol-induced gastric ulcers in rats via the HMGB1/TLR-4/NF-B signaling pathway. HMGB1 and Nuclear factor kappa (NF-B) expression, IL-1ß and Nrf2 contents showed an increase along with ulcer development, concurrent with an increase in immunohistochemical TLR-4 level. In contrast, pre-treatment with BIEE significantly reduced HMGB1 and Nuclear factor kappa (NF-B) expression levels, IL-1ß and Nrf2 contents and ulcer index value. Such protective action was further confirmed based on histological and immunohistochemical TLR-4 assays. Untargeted analysis via UPLC-ESI-Qtof-MS has allowed for the comprehensive characterization of 40 metabolites in BIEE mostly belonged to two main chemical classes, viz., flavonoids and lipids. These key metabolites, particularly flavonoids, suggesting a mediation for the anti-inflammatory and anti-ulcerogenic properties of BIEE, pose it as a promising natural drug regimen for treatment of stomach ulcers.

HPLC-ESI/MS profiling, phytoconstituent isolation and evaluation of renal function, oxidative stress and inflammation in gentamicin-induced nephrotoxicity in rats of Ficus spragueana Mildbr. & Burret.

Ficus spragueana Mildbr. & Burret (family Moraceae) was reported to have various biological activities. However, its activity in treatment of renal injury has not been investigated yet. The current study aimed to evaluate the effects of F. spragueana leaf extract on nephrotoxicity caused by gentamicin. Gentamicin is an important broad-spectrum antibiotic; nevertheless, it exhibits serious nephrotoxic adverse effects. HPLC-ESI/MS spectrometric analysis of the extract revealed the presence of 37 phenolic compounds. Moreover, five compounds were isolated from the leaf extract, and identified on the basis of spectroscopic analysis. The isolated compounds were syringic acid (1), p-coumaric acid (2), 3',5' O-dicaffeoylquinic acid (3), luteolin-8-C-ß-D glucopyranoside (orientin) (4) and 8-methoxy kaempferol-3-O-[α-L-rhamnopyranosyl (1→2) ß-D-glucopyranoside] (5). The gentamicin-induced nephrotoxicity model was used to evaluate the protective effect of F. spragueana on renal toxicity biomarkers throughout the development of acute kidney injury. Administration of extract led to improvement in kidney function through inhibition of kidney injury molecule-1, creatinine, blood urea nitrogen and total bilirubin, as well as decreasing the inflammatory markers interlukin1-beta and myeloperoxidase. Furthermore, it reduced the oxidative stress by increasing reduced glutathione and total antioxidant capacity levels while decreasing malondialdehyde and nitric oxide content, and improved renal histopathological injuries.

UPLC-qTOF-MS Phytochemical Profile and Antiulcer Potential of Cyperus conglomeratus Rottb. Alcoholic Extract.

Cyperus has been commonly used as a multi-use medicinal plant in folk medicine worldwide. The objectives of our study were to determine the different metabolites in the Cyperus conglomeratus Rottb. methanol extract, and to assess its in vivo gastroprotective effect in ethanol-induced gastric ulcer model in rats. Serum levels of galactin-3 and TNF-α were employed as biochemical markers. To pinpoint for active agents, comprehensive metabolites profiling of extract via UPLC-qTOF-MS/MS was employed. A total of 77 chromatographic peaks were detected, of which 70 were annotated. The detected metabolites were categorized into phenolic acids and their derivatives, flavonoids, stilbenes, aurones, quinones, terpenes, and steroids. Rats were divided into six groups; healthy control, ulcer control, standard drug group, and 25, 50, 100 mg/kg of C. conglomeratus treated rats. Pre-treatment with C. conglomeratus alcohol extract significantly reduced galactin-3, and TNF-α in ethanol-induced ulcer model at 25, 50, and 100 mg/kg. Further histopathological and histochemical studies revealed moderate erosion of superficial epithelium, few infiltrated inflammatory cells, and depletion of gastric tissue glycoprotein in the ulcer group. Treatment with the extract protected the gastric epithelial cells in a dose-dependent manner. It could be concluded that C. conglomeratus extract provides significant gastroprotective activity in ethanol-induced gastric ulcer and ought to be included in nutraceuticals in the future for ulcer treatment.

Selective Regulation of B-Raf Dependent K-Ras/Mitogen-Activated Protein by Natural Occurring Multi-kinase Inhibitors in Cancer Cells.

Introduction: Cancer is one of the most difficult challenges faced by humanity due to its many associated issues, such as inability to prevent diseases, treatment safety, and high mortality rate. In cancer, a variety of cellular signaling is activated to ensure malignancy transformation, angiogenesis and metastasis. The most efficient signaling pathway in cancer is mitogen-activated protein kinase (MAPK), which controls malignancy and regulates apoptosis. Methods: Four different flavonoid glycosides have been isolated from Pulicaria jaubertii using the phytochemical characterization of hydro-methanol extract. The purified glycosides (PJs) were investigated for their potential repression of cancer development using human lung epithelial cells and hepatocellular carcinoma (HCC) and compared with Sorafenib (SOR), the standard systemic drug for HCC. In PJ-treated cells, the expression profile of K-Ras, B-Raf, and P53 were detected using qRT-PCR, flow cytometry, confocal microscopy and western blot. Steady-state mRNA and levels of transforming growth factor-beta (TGF-ß) and interleukin 8 (IL-8) were monitored in the fluids media at different time points following treatment. Results: Our results showed that the qurictine glycosides (PJ-1 and PJ-9) selectively inhibited the mutant K-Ras/B-Raf proteins expression and interaction in both cancer cells; while SOR showed obvious depletion of total Raf-1 protein in cancer cells and normal cells as well. Interestingly, the combination of PJ-1 or PJ-9 with SOR exhibited restoring cell viability of normal cells via controlling Raf-1 and P53 genes expression. Further, these identified PJ agents significantly adjusted the levels of TGF-ß and IL-8 in cancer treated cells accompanied by restoring the activation of P53 expression. These findings were confirmed by docking analysis of PJs ligand and the crystal structure of K-Ras, B-Raf, and ERK transcription factor. Conclusion: The current data provide novel and natural multi-kinase inhibitors with competitive regulation of the mutant proteins; K-Ras and B-Raf and sustained MAPK signaling without any detectable toxic effect in normal cells.

Role of ashwagandha methanolic extract in the regulation of thyroid profile in hypothyroidism modeled rats.

This study aimed to evaluate the anti-hypothyroidism potential of ashwagandha methanolic extract (AME). This target was performed through induction of animal model of hypothyroidism by propylthiouracil. After 1 month from treatments, blood samples were collected for biochemical determinations, and liver and kidney were removed for the determination of oxidative stress markers and thyroid gland was removed for histopathological examination. The total phenolic compounds in the extract and the in vitro radical scavenging activity of extract were also determined. The results revealed that the induction of hypothyroidism by propylthiouracil induced a significant increase in serum TSH level but it induced significant decreases in the levels of total T3, free T3, free T4, and total T4 hormones compared with the control values. Also, serum glucose, Il-6, and body weight gain increased significantly while Il-10 and blood hemoglobin levels showed significant decrease. Induction of hypothyroidism increased also the levels of hepatic and renal MDA and NO and decreased significantly the values of GSH, GPx and Na+/ K+-ATPase. Both AME and the anti-hypothyroidism drug significantly ameliorated the changes occurred in the levels of the above parameters and improved histological picture of thyroid gland but with different degrees; where ashwagandha methanolic extract showed the strongest effect. We can conclude that ashwagandha methanolic extract treatment improves thyroid function by ameliorating thyroid hormones and by preventing oxidative stress.